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An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27m3 through the genome

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

OTHER RELATED OMICS DATASETS IN: PRJNA314771PRJNA314766PRJNA314772

ORGANISM(S): Mus musculus

PROVIDER: GSE79036 | GEO | 2016/05/02

SECONDARY ACCESSION(S): PRJNA314766

REPOSITORIES: GEO

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An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27m3 through the genome [RNA-seq]

Project description:B-cell lymphoma and melanoma harbor recurrent mutations in the gene encoding the EZH2 histone methyltransferase, but the carcinogenic role of these mutations is unclear. Here we describe a mouse model in which the most common somatic EZH2 gain-of-function mutation (Y646F in human, Y641F in the mouse) can be conditionally expressed. Expression of Ezh2Y641F in mouse B-cells or melanocytes caused high-penetrance lymphoma or melanoma, respectively. Bcl2 overexpression or p53 loss, but not c-Myc overexpression, further accelerated lymphoma progression, and expression of mutant B-Raf but not mutant N-Ras further accelerated melanoma progression. Although expression of Ezh2Y641F increased abundance of global H3K27 trimethylation (H3K27me3), it also caused a widespread redistribution of this repressive mark, including a loss of H3K27me3 associated with increased transcription at many loci. These results suggest that Ezh2Y641F induces lymphoma and melanoma through a vast reorganization of chromatin structure inducing both repression and activation of polycomb-regulated loci. B cells: 4 WT vs 4 Y641F samples, Melanoma: WT (480, 855) vs Y641F (480D, 855D) isogenic cell lines differing only for the presence of WT vs Y641F Ezh2.

2016-05-13 | E-GEOD-79035 | biostudies-arrayexpress

An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27m3 through the genome [RNA-seq]

2016-05-13 | GSE79035 | GEO

An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27m3 through the genome

Project description:An oncogenic Ezh2 mutation cooperates with particular genetic alterations to induce tumors in mice and redistributes H3K27m3 through the genome

| PRJNA314766 | ENA